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Dimethylformamide → 4-{1-[2-(2-methoxy-ethoxy)-ethyl]-1H-benzoimidazol-2-yl}-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 2230711
Notes
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Reaction equation

HRID 2230711 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)C=O.[H-].[Na+].Br[CH2:32][CH2:33][O:34][CH2:35][CH2:36][O:37][CH3:38]>O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]([CH2:32][CH2:33][O:34][CH2:35][CH2:36][O:37][CH3:38])[C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 1235321-Bromo-3,6-dioxaheptaneHCID 184646551-t-butoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane

Product 1

HCID 701494634-{1-[2-(2-methoxy-ethoxy)-ethyl]-1H-benzoimidazol-2-yl}-[1,4]diazepane-1-carboxylic acid tert-butyl esterYield 93.8%

Reagents, catalysts & solvents

1
HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

Treat a solution of 1-(t-butoxycarbonyl)-4-(1H-benzimidazol-2-yl)[1,4]diazepan (preparation 9, 0.50 g, 1.58 mmol) and dimethylformamide (10 mL) with sodium hydride (0.083 g, 2.08 mmol, 60% dispersion in oil) at room temperature. After 30 minutes, add 1-bromo-2-(2-methoxyethoxy)ethane (0.34 g, 1.88 mmol, Aldrich Chemical Company) and heat two hours at 70° C. Cool the reaction, add water (10 mL) and extract with dichloromethane (100 mL). Wash the organic phase with water, dry (Na2SO4), filter and concentrate the filtrate to afford 4-{1-[2-(2-methoxy-ethoxy)-ethyl]-1H-benzoimidazol-2-yl}-[1,4]diazepane-1-carboxylic acid tert-butyl ester (0.62 g).

Workup

  1. temperatureCool
  2. customthe reaction
  3. extractionextract with dichloromethane (100 mL)
  4. washWash the organic phase with water
  5. dry with materialdry (Na2SO4)
  6. filtrationfilter
  7. concentrationconcentrate the filtrate

Sources & evidence

ORD record
ord-963b44c8d2c549bc8b0ed15545560701
Source dataset
uspto-grants-2002_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06423704B1

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes